Our current studies in children and in the rat confirm observations on lead workers that the red cell of both man and the rat contains a monophosphoesterase specific for pyrimidines, pyrimidine 5' nucleotidase (E.C. 3.1.3.4, P5N) that dephosphorylates cytidine monophosphate (CMP) and uridine monophosphate (UMP). P5N is inhibited at low levels of blood lead with a negative linear correlation of blood lead and P5N. Pyrimidine phosphates (CMP, CDP, CTP, UMP, UDP and UTP) are present at very low levels in the red cell but accumulate with depression of P5N. Studies of the red cell nucleotide profile of lead exposed children and adults are underway. A primary deficiency of P5N as well as a high blood lead results in a basophilic stippling of the red cells, representing incompletely degraded RNA. We are investigating the hypothesis that an increased blood lead results in basophilic stippling by the feedback inhibition of ribonuclease and phosphodiesterase by the accumulation of pyrimidine nucleotides as well as by direct enzymatic inhibition by lead.